The Provocative Promise of Resveratrol

The Feb. 5, 2007 issue of Fortune magazine makes an intriguing promise. The headline proclaims: "Drink wine and live longer."

It's great publicity for wine. But the story is not really about wine, only one of its natural components.

The Fortune article, by David Stipp, focuses on the possible health benefits of resveratrol, a compound found in grapes, as well as in other foods such as peanuts, blueberries and cranberries. Sirtris Pharmaceuticals, a biotech company based in Cambridge, Mass., is working to create resveratrol-based medicines that could have the same amazing effects on human health that recent studies have found the compound can produce in mice: significantly extending their lifespan while protecting them from many diseases.

Resveratrol, a potent polyphenol found in the skins of grapes, is part of the grapevine's immune system. The compound is mobilized to fight invaders, such as molds and insects. Resveratrol becomes absorbed into red wine during the contact the fermenting juice has with the skins.

David Sinclair, a molecular biologist at Harvard University, has done extensive research on the topic. Sinclair claims resveratrol can extend the life of mice, even when the rodents are dangerously overweight. (Other recent studies have found that resveratrol can boost endurance and limit weight gain in mice, limit damage caused by a stroke, improve cardiovascular health, provide better lung function and reduce the growth of skin melanomas.)

Two years ago, Sinclair joined forces with Christoph Westphal, a biotech entrepreneur, to create Sirtris Pharmaceuticals. According to the Fortune article, venture capitalists have invested $82 million in the firm, which is already clinically testing a resveratrol drug that may help diabetics keep their blood sugar under control. More ambitiously, the company hopes that the drugs can someday cure or prevent many of the diseases linked to aging, such as adult-onset diabetes, heart disease, Alzheimer's and Parkinson's diseases--even cancer.

Unfortunately, however, it remains a mystery whether wine drinkers benefit from resveratrol, regardless of whether the drugs are found to work. In human terms, the amounts of resveratrol that were used to produce the amazing benefits in mice would require drinking hundreds--or even thousands--of glasses of wine per day. Though studies have shown that moderate wine drinkers tend to live longer than nondrinkers, it remains unknown if that's the result of consumed resveratrol having a cumulative effect. In that same study, though, heavy drinkers did not enjoy the same longevity.

Levels of resveratrol vary greatly in different types of red wine. According to Cornell researcher Leroy Creasy, who has examined the micromolar concentration of resveratrol in more than 100 American wines, grapes grown in cooler climates are believed to contain more of the substance than warmer-climate counterparts. That's because the vine will synthesize resveratrol in greater amounts where there is a greater threat, say, from an invading fungus. Creasy found that New York wines, for example, averaged 7.5 micromoles (µM) per liter of resveratrol, while California red wines tend to have about 5µM of resveratrol.

Creasy declared that any wine with a concentration of resveratrol above 10 µM was "extraordinary." A winery in Oregon even puts the resveratrol level on the back labels of its Pinot Noirs, which contain over 20µM per liter. But that's still a microscopic amount compared to the doses that were given to the mice in the headline-grabbing study late last year. The mice were given 23 milligrams of resveratrol per kilogram of body weight (one milligram equals 4.38µM).

"Should you give resveratrol to your mice that are on a high-calorie diet if you want them to live longer? Yes. Will long-term ingestion of these levels of resveratrol be safe in humans? We do not know," said Dr. Curtis Ellison of the Institute on Lifestyle and Health at Boston University School of Medicine. "Will such doses, if safe, lead to longer lifespan of humans on a high-calorie diet? Perhaps. Will such doses have a large effect on mortality in humans not on a high-calorie diet? We do not know. Are we at the Institute starting to take resveratrol pills? Not yet."

Therefore, there's more hope than reality when it comes to the health benefits of resveratrol, especially in the amounts contained in red wine. And some scientists even believe that other components of red wine are primarily responsible for the beverage's positive effects on health.

According to Roger Corder, a professor of experimental therapeutics at Queen Mary University of London and author of The Wine Diet, (which calls for a glass of red wine nightly to live longer), flavonoids in red wine called procyanidins are primarily responsible for reducing the risk of cardiovascular disease--a major factor in increased longevity. Procyanidins are antioxidants that lend pigment to grape skin and aroma to wine, and are also found in cranberries and dark chocolate. Procyanidin is believed to help keep heart tissue healthy by regulating the production of a peptide known as endothelin-1, which helps to prevent blood clots and maintain the overall health of veins and arteries. And they were effective at levels found in wine, Corder said.

One day, resveratrol may prove a great boon to human health. Thanks to the publicity, resveratrol supplements are flying off the shelves in health-food stores, though doctors caution there may be risks with the dose and purity level of the pills. But for now, the most pleasurable way to get your daily dose of resveratrol is in a glass or two of red wine.

--Additional contributions to this report by Thomas Matthews and Eric Arnold